The purpose of this K23 application is to prepare the candidate for an independent career in clinical research by allowing the investigator to acquire a comprehensive background in the neurobiology of pain and outcomes of osteoarthritis (OA) treatment. The candidate will be guided by an exceptional team of mentors, including Drs. Daniel J. Clauw, David A. Williams, Jeffrey N. Katz and James D. Myles. While population based studies demonstrate that peripheral or nociceptive input is important in generating pain in knee OA, for some patients central nervous system (CNS) factors play and equal or even more prominent role in symptom expression. The overall focus of the research project is to determine the relative contribution of different components (peripheral or central) of osteoarthritis pain. There are currently minimal data regarding the impact of central pain mechanisms on osteoarthritis, particularly with longitudinal design and multiple methods of assessment. The proposed study provides a unique opportunity to investigate these issues, using a longitudinal cohort study. The specific aims of this proposal are 1) To show that a subset of OA patients can be identified who will have subtle differences in their symptom profile suggesting that they have a "central" component to their pain, including neuropathic or somatic descriptors and/or diffuse pain on a body pain diagram 2) To show that experimental pain testing will identify knee osteoarthritis patients with a significant central pain contribution based on findings of either widespread hyperalgesia and/or deficient descending analgesic activity. 3) In a proof of concept study, we will show that central pain plays an important role in predicting failure to respond to knee arthroplasty, the definitive treatment of nociceptive pain. The results of these studies will provide new knowledge of the influence of central and peripheral components of pain to the chronic pain symptoms experienced by patients with osteoarthritis, as well as provide a more detailed understanding of etiologic relationships of pain threshold and affective disorders on chronic osteoarthritis pain and outcomes following joint replacement. The results of this study will create a new paradigm for pain and disability management in osteoarthritis and have a significant impact on the human and medical costs associated with chronic arthritis. The candidate's research career development will be enhanced through protected time for relevant coursework and mentored analyses of longitudinal data.